A host of processes, including muscle contraction, nerve conduction and sensory detectors, rely on membrane excitability in order to function. Although it is generally believed that voltage-dependent conducting pathways for ions are the basis for excitability, the molecular mechanism for this voltage dependence is not understood. This project proposes to analyze the structure of an intrinsic membrane protein that forms voltage-dependent channels in lipid bilayers. The protein (called VDAC) is now available in pure and functional form. It's structure will be studied by electron microscopy, circular dichroism, fluorescence and biochemically. These techniques will also be used to examine the conformational changes associated with channel opening and closing. Specific tests will be used to distinguish between possible models of the voltage dependent conformational change. The ultimate result will hopefully be a description of the process including the nature of the voltage sensor and the permeability barrier. This information may have general applicability to a variety of voltage dependent channels in membranes since a number of these have a voltge dependent behavior that closely resembles that of VDAC.